Naltrexone and risperidone combination sustained-release composition

Abstract

The present disclosure relates to a preparation method for a preparation, in particular, to a compound sustained-release composition of naltrexone and risperidone, and a preparation method therefor and an application thereof. The compound sustained-release composition of naltrexone and risperidone and its preparation provided in the present disclosure may be sustainably released in vitro for more than 12 weeks, the release conforms to zeroth-order approximation mode, and the release rate is stable; the suitable preparation method and parameter control are adopted in the present disclosure, so that naltrexone sustained-release microspheres and risperidone sustained-release microspheres are released synchronously, and an administration period is easier to control; further, the product provided by the present disclosure has a good effect in methamphetamine addiction tests, and can be used for preparing products for the treatment of methamphetamine addiction.

1 . A composition, comprising the following components in parts by weight:
 5-10 parts of naltrexone present in sustained-release microspheres; and   1-2 parts of risperidone present in sustained-release microspheres,   wherein the sustained-release microspheres of the risperidone are being prepared by a double emulsion-solvent evaporation method, and the risperidone sustained-release microspheres of the naltrexone are prepared by an emulsion-solvent evaporation method.   
     
     
         2 . (canceled) 
     
     
         3 . The composition according to  claim 1 , wherein the double emulsion-solvent evaporation method comprises:
 dissolving an additive in water to form an inner water phase;   dissolving risperidone and a fat-soluble polymer in an organic solvent to form an oil phase;   adding the inner water phase to the oil phase, and performing ultrasonic emulsification to obtain a primary emulsion; and   adding the primary emulsion to an aqueous solution comprising a water-soluble polymer, and evaporating the organic solvent, collecting.   
     
     
         4 . The composition according to  claim 3 , wherein
 the additive is dissolved in the water to reach a concentration of 50-300 mg/mL;   the risperidone is dissolved in the organic solvent to reach a concentration of 100-300 mg/mL, the organic solvent is selected from the group consisting of dichloromethane, ethyl acetate and the combination thereof, and the fat-soluble polymer is dissolved in the organic solvent to reach a concentration of 100-300 mg/mL; and   the primary emulsion is added to the aqueous solution at a volume ratio of (1-3):80, and the water-soluble polymer is present in the aqueous solution at a concentration of 0.1-2 wt %.   
     
     
         5 . The composition according to  claim 4 , wherein the aqueous solution further comprises sodium chloride at a concentration of ≤5 wt % or sucrose at a concentration of ≤15 wt %. 
     
     
         6 . (canceled) 
     
     
         7 . The composition according to  claim 1 , wherein the emulsion-solvent evaporation method comprises:
 dissolving naltrexone and a second fat-soluble polymer in a second organic solvent to form a second oil phase; and   adding, dropwise, the second oil phase to a second aqueous solution comprising a second water-soluble polymer, and evaporating the second organic solvent.   
     
     
         8 . The composition according to  claim 7 , wherein
 the naltrexone is dissolved in the second organic solvent to reach a concentration of 50-300 mg/mL, the fat-soluble polymer is dissolved in the second organic solvent to reach a concentration of 100-300 mg/mL, and the second organic solvent is selected from the group consisting of dichloromethane, ethyl acetate, and the combination thereof; and   the second oil phase is added to the second aqueous solution at a volume ratio of (1-3):80, the water-soluble polymer is present in the second aqueous solution at a concentration of 0.1-2 wt % and the second aqueous solution further comprises 0-10 wt % sodium chloride or 0-20 wt % sucrose.   
     
     
         9 . The composition according to  claim 1 , which further comprises a lubricant, and is provided as a tablet. 
     
     
         10 . A method for treating or relieving an addiction of amphetamine, ketamine, cocaine or cannabis in a subject, comprising administering to the subject the composition of  claim 1 . 
     
     
         11 . The composition according to  claim 3 , wherein the additive is selected from the group consisting of sodium chloride, mannitol, disodium hydrogen phosphate, sodium dihydrogen phosphate, and combinations thereof. 
     
     
         12 . The composition according to  claim 3 , wherein the fat-soluble polymer is selected from the group consisting of polylactic acid, poly(lactic-co-glycolic acid), polycaprolactone, polycarbonate, polyglycolic acid, polycyanoacrylate, polyether ester, and combinations thereof. 
     
     
         13 . The composition according to  claim 3 , wherein the water-soluble polymer is a polyvinyl alcohol. 
     
     
         14 . The composition according to  claim 4 , wherein the water-soluble polymer is present in the aqueous solution at a concentration of 0.5-0.6 wt %. 
     
     
         15 . The composition according to  claim 7 , wherein the fat-soluble polymer is selected from the group consisting of polylactic acid, poly(lactic-co-glycolic acid), polycaprolactone, polycarbonate, polyglycolic acid, polycyanoacrylate, polyether ester, and combinations thereof. 
     
     
         16 . The composition according to  claim 7 , wherein the water-soluble polymer is a polyvinyl alcohol. 
     
     
         17 . The composition according to  claim 8 , wherein the water-soluble polymer is present in the second aqueous solution at a concentration of 0.5-1 wt %. 
     
     
         18 . The composition according to  claim 9 , wherein the lubricant is selected from the group consisting of sodium stearyl fumarate, magnesium stearate, a stearic acid, and combinations thereof.